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Anticancer Drug Delivery System Utilizes Graphene Strip Transporters

By LabMedica International staff writers
Posted on 20 Jan 2015
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Image: Researchers have attached two drugs—TRAIL and Dox—onto graphene strips. TRAIL is most effective when delivered to the external membrane of a cancer cell, while Dox is most effective when delivered to the nucleus, so the researchers designed the system to deliver the drugs sequentially, with each drug hitting a cancer cell where it will do the most damage (Photo courtesy of Dr. Zhen Gu, North Carolina State University).
Image: Researchers have attached two drugs—TRAIL and Dox—onto graphene strips. TRAIL is most effective when delivered to the external membrane of a cancer cell, while Dox is most effective when delivered to the nucleus, so the researchers designed the system to deliver the drugs sequentially, with each drug hitting a cancer cell where it will do the most damage (Photo courtesy of Dr. Zhen Gu, North Carolina State University).
The ongoing search by cancer researchers for targeted drug delivery systems has generated a novel approach that uses graphene strips to transport simultaneously the anticancer agents TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) and Dox (doxorubicin).

Cancer cells can develop resistance to chemotherapy drugs, but are less likely to develop resistance when multiple drugs are delivered simultaneously. However, different drugs target different parts of the cancer cell. For example, the protein drug TRAIL is most effective against the cell membrane, while Dox is most effective when delivered to the nucleus.

Although in use for more than 40 years as a primary chemotherapy drug, Dox is known to cause serious heart problems. To prevent these, doctors may limit the amount of Dox given to each patient so that the total amount a patient receives over her or his entire lifetime is 550 milligrams per square meter, or less. Furthermore, the necessity to stop treatment to protect the patient from heart disease may diminish the usefulness of Dox in treating cancer. TRAIL is a cytokine that is produced and secreted by most normal tissue cells. It causes apoptosis primarily in tumor cells by binding to certain death receptors. Since the mid-1990s it has been used as the basis for several anticancer drugs, but was not been found to have any significant survival benefit.

Investigators at North Carolina State University (Raleigh, USA) and the University of North Carolina (Chapel Hill, USA) have developed a sequential and site-specific delivery technique that first delivers TRAIL to cancer cell membranes and then penetrates the membrane to deliver Dox to the nucleus. In addition, they reported in the December, 15, 2014, online edition of the journal Advanced Materials that TRAIL actively targets molecules that allow it to bind directly to the surface of cancer cells.

The new approach is based on graphene strips loaded with Dox to which TRAIL has been bound by a chain of amino acids. The strips are able to penetrate to the site of a tumor via leaks in blood vessels caused by the cancer. Once in the proximity of the tumor, receptors on the surface of the cancer cells bind TRAIL. Enzymes on the surface of the cancer cells then dissolve the bonds linking TRAIL to the graphene strip, which allows the cells to absorb the Dox-laden graphene. TRAIL remains on the cell surface, where it triggers the process of apoptosis resulting in the destruction of the tumor.

"These drug-rich graphene strips are introduced into the bloodstream in solution, and then travel through the bloodstream like nanoscale flying carpets," said senior author Dr. Zhen Gu, assistant professor in the joint biomedical engineering program at North Carolina State University and the University of North Carolina. "We have demonstrated that TRAIL itself can be used to attach a drug delivery system to a cancer cell, without using intervening material—which is something we did not know, and because graphene has a large surface area, this technique enhances our ability to apply TRAIL to its target on cancer cell membranes."

Related Links:

North Carolina State University
University of North Carolina


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